Identification of Chd7 and Top2b regulated genes in cerebellar granule neurons
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE76975 | GEO | 2017/01/20
SECONDARY ACCESSION(S): PRJNA309165
REPOSITORIES: GEO
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Project description:We mapped the binding sites of Chd7 in cerebellar granule cells, and compared with the pattern of H3K27ac. To examine the impact of Chd7 loss to Top2b binding, we mapped the binding sites of Top2b in control and Chd7 mutant cells
2017-01-20 | GSE93719 | GEO
Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
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Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
2022-10-11 | GSE212438 | GEO
Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
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Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
2023-04-25 | GSE218685 | GEO
Project description:The functional and transcriptional maturation of neurons is a prolonged process that extends well beyond mitotic exit and terminal fate commitment of progenitors. The differentiation of cerebellar granule neurons (CGNs) in the postnatal mouse cerebellum provides a useful model to identify chromatin mechanisms that orchestrate temporal changes in transcription as postmitotic CGNs mature. Here we report that CGN maturation is associated with dynamic changes in the genomic distribution of histone H3 lysine 27 trimethylation (H3K27me3), a modification best known for its role in repressing alternative fates during cell specification. H3K27me3 is gained rapidly in newly postmitotic CGNs at progenitor-expressed genes that are repressed in neurons. H3K27me3 is lost more gradually at the promoters of a subset of neuronal genes that are transcriptionally induced upon CGN maturation. The loss of H3K27me3 is facilitated by the lysine demethylase KDM6B, and genes that are induced in maturing CGNs show impaired expression in the cerebellum of conditional KDM6B knockout mice. Genes that lose H3K27me3 gain H3K27 acetylation and binding of the pro-maturation ZIC1/2 transcription factors, suggesting that developmental loss of H3K27me3 may be required to permit the onset of transcriptional maturation. Interestingly, pharmacological inhibition of the H3K27 methyltransferase EZH2 in early postmitotic CGNs not only blocked the repression of progenitor genes but also impaired the induction of mature CGN genes. These data show that regulation of H3K27me3 functions in developing postmitotic neurons beyond the period of cell fate commitment to regulate the dynamics of gene expression programs that underlie functional neuronal maturation.
2023-04-28 | GSE230712 | GEO
Project description:We performed ATAC-seq to profile the open chromatin lanscape in primary Chd7 WT and mutant GNPs. By analyzing the differentiate peaks between WT and mutant, we identified Chd7-dependent maintance of open chromatin at many neuronal genes.
2017-01-20 | GSE76984 | GEO
Project description:Mutation of the gene encoding the ATP-dependent chromatin remodeler CHD7 causes CHARGE syndrome. The mechanisms underlying the neurodevelopmental deficits associated with the syndrome, which include cerebellar hypoplasia, developmental delay, coordination problems and autistic features, are not known. CHD7 is expressed in neural stem and progenitor cells, but its role in neurogenesis during brain development remains unknown. Here we show that deletion of Chd7 from cerebellar granule cell precursors (GCps) in the mouse results in reduced GCp proliferation, cerebellar hypoplasia, developmental delay and motor deficits. Genome-wide expression profiling revealed downregulated Reln gene expression in Chd7-deficient GCps. Recessive RELN mutations is associated with severe cerebellar hypoplasia in humans. We provide molecular and genetic evidence that reduced Reln expression contributes substantially to the GCp proliferative defect and cerebellar hypoplasia in GCp-specific Chd7 mouse mutants. Finally, we show that CHD7 is necessary for the maintenance of an open, accessible chromatin state at the Reln locus. Taken together, this study shows that Reln gene expression is regulated by chromatin remodeling, identifies CHD7 as a previously unrecognized upstream regulator of Reln and provides the first evidence that a mammalian CHD protein controls brain development by modulating chromatin accessibility in neuronal progenitors in vivo.
2017-01-01 | GSE90466 | GEO
Project description:Dendrite and synapse development are critical for establishing appropriate neuronal circuits, and disrupted timing of these events can alter connectivity leading to disordered neural function. In early postnatal development of cerebellar granule neurons (CGNs), the expression of many genes is temporally regulated. Further, NFI (Nuclear Factor I) proteins have been shown to play important roles in the regulation of gene expression in developing CGNs. To identify NFI-regulated genome-wide targets involved in late maturation of mouse CGNs, we performed two groups of microarray expression analysis: (1) temporal expression arrays using 1.5 and 6 day cultures of mouse CGNs representing immature and more mature CGNs, respectively, which identified 844 Temporal-Up or Down genes; and (2) NFI-regulated genes in 6 day CGN cultures that were infected at the time of plating with lentiviral vectors expressing either NFI dominant repressor (NFI-EnR) or EnR control protein. This identified 686 NFI-Up (NFI-EnR down-regulated) or NFI-Down (NFI-EnR up-regulated) genes. Overlap analysis identified 212 temporal genes that were regulated by NFI. These results indicated that NFI plays a pivotal role in the regulation of late CGN maturation. For temporal arrays, mouse CGN progenitors were purified from P6 mouse cerebellum and cultured for either 1.5 or 6 days. Three biological replicates were analyzed for each time point. For NFI arrays, CGN progenitors from P6 mice were transduced upon plating with either NFI-EnR or EnR control lentivirus and cultured 6 days. Four pairs of biological replicates were performed.
2012-11-07 | E-GEOD-42018 | biostudies-arrayexpress
Project description:Dendrite and synapse development are critical for establishing appropriate neuronal circuits, and disrupted timing of these events can alter connectivity leading to disordered neural function. In early postnatal development of cerebellar granule neurons (CGNs), the expression of many genes is temporally regulated. Further, NFI (Nuclear Factor I) proteins have been shown to play important roles in the regulation of gene expression in developing CGNs. To identify NFI-regulated genome-wide targets involved in late maturation of mouse CGNs, we performed two groups of microarray expression analysis: (1) temporal expression arrays using 1.5 and 6 day cultures of mouse CGNs representing immature and more mature CGNs, respectively, which identified 844 Temporal-Up or Down genes; and (2) NFI-regulated genes in 6 day CGN cultures that were infected at the time of plating with lentiviral vectors expressing either NFI dominant repressor (NFI-EnR) or EnR control protein. This identified 686 NFI-Up (NFI-EnR down-regulated) or NFI-Down (NFI-EnR up-regulated) genes. Overlap analysis identified 212 temporal genes that were regulated by NFI. These results indicated that NFI plays a pivotal role in the regulation of late CGN maturation.
2012-11-07 | GSE42018 | GEO